It is now apparent that subtype C has become the most prevalent HIV-1 genetic subtype globally, with epicenters in souther Africa, India and southwestern China. It is anticipated that infection by subtype C viruses will dominate well into the next century, thus making the choice of these strains for vaccine work timely and highly relevant. We have made the decision to select subtype C isolates from China and southern Africa for our studies, with the long-term goal of conducting vaccine trials in these countries when suitable products are made. We will place emphasis on viruses that are non-syncytium-inducing and macrophage tropic since these are the strains that utilize the principal co-receptor CCR5 and are preferentially transmitted. Lastly, based on subtype C env, we will develop a new SHIV/macaque model to test multiple immunogens and vaccine concepts. Three specific aims are proposed in this project: 1. Genotypic, phenotypic, and antigenic characterization of subtype C isolates of HIV-1 and selection of vaccine strains. 2. Subtype C envelope expression and modification. 3. Construction of subtype C envelope SHIV's and testing in macaques.